Volume 11 · Issue 02 · 2022

While malaria morbidity and mortality have declined since 2000, viral central nervous system infections appear to be an important, underestimated cause of coma in malaria-endemic Eastern Africa. We aimed to describe the etiology of non-traumatic comas in young children in Benin, as well as their management and early outcomes, and to identify factors associated with death .

From March to November 2018, we enrolled all HIV-negative children aged between 2 and 6 years, with a Blantyre Coma Score ≤ 2, in this prospective observational study. Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol, including blood cultures, malaria diagnostics, and cerebrospinal fluid analysis using multiplex PCR. To determine factors associated with death, univariate and multivariate analyses were performed.

From 3244 admissions, 84 children were included: malaria was diagnosed in 78, eight of whom had a viral or bacterial co-infection. Six children had a non-malarial infection or no identified cause. The mortality rate was 29.8% (25/84), with 20 children dying in the first 24 h. Co-infected children appeared to have a poorer prognosis. Of the 76 children who consulted a healthcare professional before admission, only 5 were prescribed adequate antimalarial oral therapy. Predictors of early death were jaundice or increased bilirubin [odd ratio (OR)= 8.6; 95% confidential interval (CI): 2.03–36.1] and lactate > 5 mmol/L (OR= 5.1; 95% CI: 1.49–17.30). Antibiotic use before admission (OR = 0.1; 95% CI: 0.02–0.85) and vaccination against yellow fever (OR= 0.2, 95% CI: 0.05–0.79) protected against mortality.

Infections were found in all children who died, and cerebral malaria was by far the most common cause of non-traumatic coma. Missed opportunities to receive early effective antimalarial treatment were common. Other central nervous system infections must be considered in their management. Some factors that proved to be protective against early death were unexpected.

Infectious disease diagnostics often requires sensitive molecular assays that identify at both genus and species levels. For large scale screening, such as malaria screening for elimination, diagnostic assay can be a challenge, as both the throughput and cost of the assay must be considered. The requirement of nucleic acid extraction hampers the throughput of most molecular assays. Co-amplification of multiple species or multiplex identification either can result in missed diagnosis or are too costly for large-scale screening. A genus-and species-specific diagnostic assay with simplified procedure, high sensitivity and throughput is still needed. This study aimed to develop a sensitive and high-throughput approach for large-scale infectious disease screening.

We developed multi-section Capture and Ligation Probe PCR (mCLIP-PCR) for the direct detection of RNA without extraction and reverse transcription. Multiple tailed sandwich hybridization probes were used to bind at genus-and species-specific sections of the target RNA to cooperatively capture the target onto a 96-well plate. After enzymatic ligation of the bound probes, a single-stranded DNA formed at each section with distinct tail sequence at the ends. They were separately PCR-amplified with primers corresponding to tail sequences for genus or species identification. We applied the method to the active screening of Plasmodium infections of 4,580 asymptomatic dried blood spot samples collected in malaria endemic areas and compared the results with standard qPCR using linear regression.

With multi-section cooperative capture but separate amplification strategy, we accurately identified genus Plasmodium and species P. falciparum and P. vivax without RNA extraction, with favorable sensitivities among the published reports. In the active screening, our method identified all 53 positive infections including two mixed infections, and two P. vivax infections that were missed by standard qPCR.

mCLIP-PCR provides a sensitive and high-throughput approach to large-scale infectious disease screening with low cost and labor, making it a valuable tool for malaria elimination in endemic region.

New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by WHO. Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations. In this study, we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa.

Mosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon (Njombe-Penja, Nkolondom, and Mangoum), the Democratic Republic of Congo (Ndjili-Brasserie), Ghana (Obuasi), and Uganda (Mayuge). Using the CDC bottle test, we compared the effect of three different solvents (ethanol, acetone, MERO) on the efficacy of neonicotinoids against Anopheles gambiae s.l. In addition, TaqMan assays were used to genotype key pyrethroid-resistant markers in An. gambiae and odds ratio based on Fisher exact test were used to evaluate potential cross-resistance between pyrethroids and clothianidin.

Lower mortality was observed when using absolute ethanol or acetone alone as solvent for clothianidin (11.4-51.9% mortality in Nkolondom, 31.7-48.2% in Mangoum, 34.6-56.1% in Mayuge, 39.4-45.6% in Obuasi, 83.7-89.3% in Congo and 71.1-95.9% in Njombe pendja) compared to acetone+ MERO for which 100% mortality were observed for all the populations. Similar observations were done for imidacloprid and acetamiprid. Synergist assays (PBO, DEM and DEF) with clothianidin revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility. A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors (OR= 0.5; P= 0.02). However, the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes (OR= 2.10; P= 0.013).

This study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting to lower mortality, thus possibly overestimating resistance, whereas the MERO consistently showed a greater efficacy of neonicotinoids but it could prevent to detect early resistance development. Therefore, we recommend monitoring the susceptibility using both acetone alone and acetone+ MERO (4 µg/ml for clothianidin) to capture the accurate resistance profile of the mosquito populations.

Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR).

The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods.

We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP.

In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH.

The ongoing COVID-19 pandemic hit South America badly with multiple waves. Different COVID-19 variants have been storming across the region, leading to more severe infections and deaths even in places with high vaccination coverage. This study aims to assess the spatiotemporal variability of the COVID-19 pandemic and estimate the infection fatality rate (IFR), infection attack rate (IAR) and reproduction number (R₀) for twelve most affected South American countries.

We fit a susceptible-exposed-infectious-recovered (SEIR)-based model with a time-varying transmission rate to the reported COVID-19 deaths for the twelve South American countries with the highest mortalities. Most of the epidemiological datasets analysed in this work are retrieved from the disease surveillance systems by the World Health Organization, Johns Hopkins Coronavirus Resource Center and Our World in Data. We investigate the COVID-19 mortalities in these countries, which could represent the situation for the overall South American region. We employ COVID-19 dynamic model with-and-without vaccination considering time-varying flexible transmission rate to estimate IFR, IAR and R₀ of COVID-19 for the South American countries.

We simulate the model in each scenario under suitable parameter settings and yield biologically reasonable estimates for IFR (varies between 0.303% and 0.723%), IAR (varies between 0.03 and 0.784) and R₀ (varies between 0.7 and 2.5) for the 12 South American countries. We observe that the severity, dynamical patterns of deaths and time-varying transmission rates among the countries are highly heterogeneous. Further analysis of the model with the effect of vaccination highlights that increasing the vaccination rate could help suppress the pandemic in South America.

This study reveals possible reasons for the two waves of COVID-19 outbreaks in South America. We observed reductions in the transmission rate corresponding to each wave plausibly due to improvement in nonpharmaceutical interventions measures and human protective behavioral reaction to recent deaths. Thus, strategies coupling social distancing and vaccination could substantially suppress the mortality rate of COVID-19 in South America.

Nucleic acid test (NAT) could effectively control the spread of COVID-19 caused by large-scale sports competitions. However, quantitative analysis on the appropriate frequency of NAT is scarce, and the cost-effectiveness and necessity of high-frequency NAT remain to be fully explored and validated. This study aims to optimize the COVID-19 surveillance strategies through cost-effectiveness analysis for the Tokyo 2020 Olympic Games and the upcoming Beijing 2022 Olympic Winter Games.

A total of 18 scenarios were designed regarding the NAT frequency, symptom monitoring, and strengthening close-contact control. An agent-based stochastic dynamic model was used to compare the cost-effectiveness of different NAT scenarios and optimize the surveillance strategies. The dynamics of the proposed model included the arrival and departure of agents, transmission of the disease according to Poisson processes, and quarantine of agents based on regular NATs and symptom onset. Accumulative infections, cost, and incremental cost-effectiveness ratio (ICER) were simulated in the frame of the model. ICER was used to compare the cost-effectiveness of different scenarios. Univariate sensitivity analysis was performed to test the robustness of the results.

In Scenario 16, where the competition-related personnel (CRP) received NAT daily and national sports delegation (NSD) with quarantined infections accepted an additional NAT daily, accumulative infection was 320.90 (90 initial infections), the total cost was (United States Dollar) USD 8 920 000, and the cost of detecting out each infection was USD 27 800. Scenario 16 would reduce the total cost by USD 22 570 000 (avoid 569.61 infections), USD 1 420 000 (avoid 47.2 infections) compared with Scenario 10 (weekly NAT, strengthened close contact control) and Scenario 7 (daily NAT, no strengthened close contact control), respectively. Sensitivity analysis showed that the result was most sensitive to the change in basic reproductive number.

High-frequency NATs such as bidaily, daily, and twice a day were cost-effective. NAT daily for CRP with strengthening close-contact control could be prioritized in defense against COVID-19 at large-scale sports competitions. This study could assist policymakers by assessing the cost-effectiveness of NAT scenarios and provide the host country with an optimal COVID-19 surveillance strategy.

With the progress of globalization, international mobility increases, greatly facilitating cross-border transmission of respiratory infectious diseases (RIDs). This study aimed to analyze the epidemiological characteristics and factors influencing imported RIDs, with the goal of providing evidence to support adoption of high-tech, intel-ligent methods to early find imported RIDs and prevent their spread in China.

We obtained data of imported RIDs cases from 2014 to 2018 from the Inbound Sentinel Network of Customs and the National Notifiable Diseases Reporting System in China. We analyzed spatial, temporal, and population distribution characteristics of the imported RIDs. We developed an index to describe seasonality. Pearson correlation coefficients were used to examine associations between independent variables and imported cases. Data analyses and visualizations were conducted with R software.

From a total of 1 409 265 253 inbound travelers, 31 732 (2.25/100 000) imported RIDs cases were reported. RIDs cases were imported from 142 countries and five continents. The incidence of imported RIDs was nearly 5 times higher in 2018 (2.81/100 000) than in 2014 (0.58/100 000). Among foreigners, incidence rates were higher among males (5.32/100 000), 0–14-year-olds (15.15/100 000), and cases originating in Oceania (11.10/100 000). The vast majority (90.3%) of imported RIDs were influenza, with seasonality consistent with annual seasonality of influenza. The spatial distribution of imported RIDs was different between Chinese citizens and foreigners. Increases in inbound travel volume and the number of influenza cases in source countries were associated with the number of imported RIDs.

Our study documented importation of RIDs into China from 142 countries. Inbound travel poses a significant risks bringing important RIDs to China. It is urgent to strengthen surveillance at customs of inbound travelers and establish an intelligent surveillance and early warning system to prevent importation of RIDs to China for preventing further spread within China.

Though the utilization of traditional medicine has been proposed for modern drug research and development (R&D), limited research has discussed its feasible paths. In this commentary, we summarized key factors for new drug R&D under limited resources by reviewing China’s discovery of artemisinin, and raised suggestions to utilize traditional medicines in low-and middle-income countries (LMICs).

We suggested that systematic utilization of traditional medicine, outstanding synergy of research units at all levels and timely information-sharing mechanism should be achieved to establish a comprehensive and efficient R&D system, especially under low-resource settings. In the case of artemisinin discovery, Chinese scientists integrated documented traditional medicine experiences and modern approaches to develop drug candidates timely. Due to limited R&D resources, China adopted a collaborative way, motivating nearly all domestic research units at different levels, to develop antimalarial products. Moreover, the excellent synergy among all units through efficient information-sharing mechanisms greatly avoided work repetition and accelerated the R&D process.

Traditional medicines inspires drug discoveries in LMICs, while a comprehensive and efficient R&D system could accelerate its R&D process and save investment. The discovery of artemisinin in China gave a reliable pattern to promote sustainable development of traditional medicines and a good example to realize R&D of traditional medicine under low-resource settings.

我怀着深深的悲痛和悲痛获悉，世卫组织被忽视热带疾病控制司司长Mwelecele Ntuli Malecela博士在长期患病后于2022年2月10日去世，享年58岁。我谨对著名科学家和老朋友姆韦莱·马莱塞拉博士的不幸去世表示最深切的哀悼。她是非洲最知名和最受尊敬的女性研究人员、科学家和公共卫生领导人之一。